The fundamental principles of image-guided interventions are tumor detection, navigation, delivery and control of the intervention. The powerful union of focused ultrasound (FUS) and magnetic resonance imaging (MRI) or MR-guided FUS allows for accurate detection of the disease, measurement of tissue temperature changes and confirmation of thermally induced tissue changes. Such an integrated delivery system can provide a non-invasive treatment method for many tumors. We have designed, developed and tested integrated systems for use of FUS, which are currently in clinical trials for treatment of breast fibro-adenomas and uterine leiomyomas, led by this same team of investigators. Prostate cancer represents one of the most significant challenges in medicine and public health, facing the US healthcare system today. It presents an ideal model for this non-invasive thermal ablation method or FUS surgery. It is a discrete tumor, which is accessible, and of an appropriate size for targeted delivery of a focal treatment. MR is uniquely suited to imaging the prostate as it allows excellent visualization of the gland, its substructure and all surrounding tissues. MRI guidance can provide targeting, controlled delivery of the thermal energy and help prevent damage to the surrounding critical anatomic structures. In the proposed research, our goal is to develop an interactive comprehensive MR image-guided FUS system for treatment of localized prostate cancer. Our specific aims are 1) To test transrectal device for MR guided thermal therapy in the prostate. 2) To use MRI to define the target prostate lesions, on the basis of multi-parametric MR image data sets. These images will be analyzed, by registration and segmentation, for target definition and navigation, and then integrated into an on-line thermal dose planning system. 3) To perform phase I human trials to test the feasibility, safety and efficacy of MRgFUS for prostate cancer. These will be done prior to radical prostatectomy, with resulting pathological validation of thermal necrosis. The challenge is to increase the information content of intraoperative image data by using multimodal features, while at the same time preserving the interactivity and the near-real time features of intraoperative imaging. When this can be achieved, the precise delivery of FUS to maximize tumor ablation, and minimize side effects will be possible. Thus, at the conclusion of this project we will be poised to begin larger phase II/III clinical trials, with an industrial partner leading to commercial development of a device for further trials.